RESUMEN
CONTEXT: Autoimmune gastritis and pernicious anemia are common autoimmune disorders, being present in up to 2% of the general population. In patients with type 1 diabetes or autoimmune thyroid disease, the prevalence is 3- to 5-fold increased. This review addresses the epidemiology, pathogenesis, diagnosis, clinical consequences, and management of autoimmune gastritis in type 1 diabetic patients. SYNTHESIS: Autoimmune gastritis is characterized by: 1) atrophy of the corpus and fundus; 2) autoantibodies to the parietal cell and to intrinsic factor; 3) achlorhydria; 4) iron deficiency anemia; 5) hypergastrinemia; 6) pernicious anemia may result from vitamin B12 deficiency; and 7) in up to 10% of patients, autoimmune gastritis may predispose to gastric carcinoid tumors or adenocarcinomas. This provides a strong rationale for screening, early diagnosis, and treatment. The management of patients with autoimmune gastritis implies yearly determination of gastrin, iron, vitamin B12 levels, and a complete blood count. Iron or vitamin B12 should be supplemented in patients with iron deficiency or pernicious anemia. Whether regular gastroscopic surveillance, including biopsies, is needed in patients with autoimmune gastritis/pernicious anemia is controversial. The gastric carcinoids that occur in these patients generally do not pose a great threat to life, whereas the danger of developing carcinoma is controversial. Nevertheless, awaiting a consensus statement, we suggest performing gastroscopy and biopsy at least once in patients with autoantibodies to the parietal cell, iron-, or vitamin B12-deficiency anemia, or high gastrin levels. CONCLUSION: The high prevalence of autoimmune gastritis in type 1 diabetic patients and its possible adverse impact on the health of the patient provide a strong rationale for screening, early diagnosis, periodic surveillance by gastroscopy, and treatment.
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Diabetes Mellitus Tipo 1/complicaciones , Gastritis Atrófica/complicaciones , Anemia Perniciosa/complicaciones , Anemia Perniciosa/inmunología , Anemia Perniciosa/patología , Anemia Perniciosa/terapia , Autoanticuerpos/sangre , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 1/terapia , Gastritis Atrófica/inmunología , Gastritis Atrófica/patología , Gastritis Atrófica/terapia , HumanosRESUMEN
This review addresses the current concepts in our understanding of the epidemiology, mechanisms, symptoms, clinical consequences, diagnosis and treatment of delayed gastric emptying in patients with diabetes. Upper gastrointestinal symptoms, particularly postprandial fullness, nausea, vomiting and abdominal bloating, occur in 30-50% of patients with diabetes. The use of scintigraphic techniques, and more recently breath test, has shown that as many as 50% of diabetic patients have gastroparesis. Diabetic gastroparesis comprises a decrease in fundic and antral motor activity, a reduction or a lack of the interdigestive migrating motor complex, gastric dysrhythmias, and pylorospasms. The mechanisms involved include: autonomic neuropathy, acute hyperglycaemia, and abnormalities in gastrointestinal hormones and neuropeptides. Other possible contributing factors such as hypothyroidism and H. pylori infection are discussed as well. Because treatment is possible by means of dietary advise, prokinetics or surgical procedures, it is important to identify risk factors for and to diagnose gastroparesis to prevent morbidity by controlling gastrointestinal symptoms, and to enhance glucoregulation. Understanding the current advances is key to the development of novel therapeutic strategies and for making rational choices in the management of diabetic gastroparesis.
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Complicaciones de la Diabetes/fisiopatología , Diabetes Mellitus/fisiopatología , Motilidad Gastrointestinal/fisiología , Gastroparesia/epidemiología , Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/cirugía , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Duodeno/fisiología , Duodeno/fisiopatología , Ingestión de Alimentos , Gastrectomía , Humanos , Yeyuno/cirugía , Estómago/fisiología , Estómago/fisiopatologíaRESUMEN
OBJECTIVE: The aim of this study was to compare oxidative stress status (OSS) with blood glucose and lipid changes during the fasting, postprandial and postabsorptive phases in type 1 diabetes mellitus. METHODS: Twenty-three patients on intensive insulin treatment received a standard fat-rich breakfast and lunch. OSS was monitored at fasting (F), just after the post-breakfast glycemia peak (BP) (identified by continuous subcutaneous glucose monitoring), 3.5-h post-breakfast (B3.5), just after the post-lunch peak (LP), just after the post-lunch dale (LD) and 5 hours after lunch (L5). RESULTS: Whereas whole blood glutathione and plasma protein thiols increased in the postprandial period (from 6.52 +/- 1.20 (F) to 7.08 +/- 1.45 micromol/g Hb (BP), p = 0.005), ascorbate decreased gradually from 44 +/- 17 (F) to 39 +/- 19 micromol/L (LD), p = 0.015. Retinol and alpha-tocopherol also decreased from 27.1 +/- 7.0 (F) to 25.3 +/- 5.2 micromol/L (BP), p = 0.005. Uric acid decreased later, from 213 +/- 77 (BP) to 204 +/- 68 micromol/L (B3.5), p = 0.01, but then increased in LP (231 +/- 70 micromol/L) and LD to values higher than F (215 +/- 64, micromol/L, p = 0.01). Malondialdehyde increased gradually from 1.02 +/- 0.36 (F) to a maximum of 1.14 +/- 0.40 micromol/L (LP). In the postabsorptive phase (L5) all parameters except for thiols reverted to fasting concentrations. CONCLUSIONS: In type 1 diabetes lipid peroxidation increases during the postprandial phase in parallel to glucose and triglyceride changes. Blood antioxidants, however, followed diverse patterns of change.
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Antioxidantes/metabolismo , Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Lípidos/sangre , Estrés Oxidativo/fisiología , Absorción , Adulto , Área Bajo la Curva , Ayuno/sangre , Femenino , Alimentos , Glutatión/sangre , Humanos , Insulina/metabolismo , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Periodo Posprandial , Triglicéridos/sangreRESUMEN
OBJECTIVE: To investigate a possible association of BMI with retinopathy and neuropathy in type 1 diabetes. Retinopathy and neuropathy may not only be related to glycemic control and diabetes duration but also to blood pressure and BMI. RESEARCH DESIGN AND METHODS: A total of 592 type 1 diabetic patients without nephropathy were studied (M/F: 324/268; age: 41 +/- 12 years; duration: 19 +/- 11 years; HbA(1c) [A1C]: 7.9 +/- 1.1%). Patients were subdivided according to BMI: 168 men and 146 women with BMI <25 kg/m(2), and 156 men and 122 women with BMI > or =25 kg/m(2). Retinopathy was examined by fundoscopy and neuropathy by electromyography. RESULTS: Hypertension (>130/85 mmHg) was present in 40%, retinopathy in 53%, and neuropathy in 43% of patients. Overweight subjects had more retinopathy (63 vs. 45%, P < 0.0001, odds ratio [OR] = 2.1) and neuropathy (49 vs. 38%, P = 0.008, OR = 1.6) than normal-weight patients. Patients with retinopathy were older (45 +/- 12 vs. 37 +/- 11 years, P < 0.0001) and had a longer diabetes duration (25 +/- 10 vs. 12 +/- 8 years, P < 0.0001), a higher A1C (8.0 +/- 1.1 vs. 7.7 +/- 1.1%, P = 0.001), and a higher BMI (25.8 +/- 4.1 vs. 24.7 +/- 4.2 kg/m(2), P = 0.001) than individuals without retinopathy. The same results are found in neuropathy. Logistic regression analysis showed that diabetes duration (beta = 0.15, P < 0.0001), blood pressure (beta = 0.22, P = 0.0047), and A1C (beta = 0.24, P = 0.01), but not BMI, lipid levels, sex, or age, were independent risk factors for retinopathy. Likewise, duration (beta = 0.05, P < 0.0001), age (beta = 0.04, P = 0.0001), A1C (beta = 0.35, P < 0.0001), and sex (beta = 0.74, P = 0.0001) but not BMI, lipid levels, or hypertension were independently associated with neuropathy. Men had more neuropathy than women (50 vs. 34%, P < 0.0001, OR = 1.9). Leptin and adiponectin levels did not differ between individuals with or without microvascular complications. CONCLUSIONS: Retinopathy and neuropathy are more prevalent in overweight (BMI > or =25 kg/m(2)) type 1 diabetic subjects. However, logistic regression analysis showed that diabetes duration and A1C remain the main determinants for retinopathy and neuropathy.
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Diabetes Mellitus Tipo 1/complicaciones , Angiopatías Diabéticas/complicaciones , Neuropatías Diabéticas/epidemiología , Retinopatía Diabética/epidemiología , Obesidad/complicaciones , Adulto , Presión Sanguínea , Índice de Masa Corporal , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad RelativaRESUMEN
BACKGROUND: Pre-prandial glucose gives insufficient information on glycemic excursions throughout the day. We aimed to test a continuous subcutaneous glucose-monitoring device (GlucoDay) to describe postprandial glucose changes. METHODS: In 23 T1DM patients, 24-h GlucoDay registrations were started about 14 h before receiving a standard breakfast B and 3 h later lunch L. RESULTS: The 3-min glucose values were computed into parameters describing the postprandial changes after B and L. Two-hour glucose was higher after B (243 +/- 69 vs 180 +/- 79 mg/dL after L, p < 0.0001). Maximum glycemia (313 +/- 105 mg/dL after B and 304 +/- 119 after L, p < 0.0001) was higher and was reached after 78 and 57 min respectively. Three-hour AUC was higher but 30-min AUC was lower after B (5725 +/- 2414 vs 7488 +/- 2208 min mg/dL after L, p = 0.004). Glucose spikes (maximum peak minus fasting plasma glucose) were similar after B and L but the difference between maximum and minimum values was smaller after B (165 +/- 110 vs 219 +/- 115 mg/dL after L, p = 0.020). Duration of hyperglycemic periods >200, 140 or 126 mg/dL were not different after B or L, but time spent at glucose <100 mg/dL was longer after L (p < 0.0001). CONCLUSIONS: These results illustrate the use of subcutaneous glucose registration to characterize postprandial glycemia patterns in T1DM. Application of such methods to evaluate this and other clinical situations in DM can lead to therapeutic and dietary adjustments and ultimately improve glycemic control.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Monitoreo Ambulatorio/métodos , Periodo Posprandial , Adulto , Anciano , Presión Sanguínea , Índice de Masa Corporal , Ayuno , Hemoglobina Glucada/análisis , Humanos , Insulina/uso terapéutico , Lípidos/sangre , Persona de Mediana Edad , Monitoreo Ambulatorio/instrumentación , Análisis de RegresiónRESUMEN
Chronic Mg depletion in T1dm has been linked to polyneuropathy (PNP). Short term Mg supplementation has suggested a decrease in pathological EMG signs typical for PNP. The aim of this study is to determine if long term supplementation under stable metabolic control can normalize the Mg status and influence the natural evolution of PNP. 110 T1dm (60 M,50 W) with chronic Mg depletion (erythrocyte Mg < 2.3 mMol/l) were randomised to receive 300 mg Mg++ daily or no supplement for a period of 5 years. Follow-up was organized by the same diabetologist: HbA1c, renal function and Mg status every 3 months, electromyography (EMG) and clinical neurological control with staging every year. Drop-out was decided for recurrent DKA, diseases or drugs interfering with Mg status or side-effects of Mg treatment. 97 patients (53 M,44 W) finished the study: 49 (27 M,22W) were supplemented (group A) and 48 (26 M,22 W) served as controls (group B). At the start there were no significant differences between both groups. HbA1c after 5 years (A:7.80% sd 0.80, B:7.75% sd 0.75) was not significantly different from the start. Erythrocyte Mg (Mg rbc) rose significantly (p < 0.0001) in group A to normal levels but remained low in group B. Staging of PNP after 5 years shows a decrease in 39%, statu quo in 49% and a worsening in 12% in group A and 8,31 and 61% respectively in group B (Fisher Exact test: p < 0.0001). Normalization of EMG signs was only seen in incipient PNP. Logistic regression analysis shows that longer duration of diabetes (p < 0.006) and low Mgrbc (p < 0.05) are the major determinants of PNP evolution. Under stable metabolic control long term Mg supplementation is able to restore a normal Mg status and influence favourably the natural evolution of PNP as compared to non supplemented T1dm controls.
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Diabetes Mellitus Tipo 1/dietoterapia , Neuropatías Diabéticas/dietoterapia , Suplementos Dietéticos , Magnesio/metabolismo , Adulto , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: To investigate the impact of Vitamin E on lipids and peroxidation during statin treatment. RESEARCH DESIGN AND METHODS: T1DM patients with high cholesterol received Atorvastatin 20mg with either placebo (group AP, n = 11) or d-alpha-tocopherol 750 IU (group AE, n = 11) daily. They were monitored for blood biochemistry, low-density lipoprotein (LDL) subfractions and lipid peroxidation at inclusion and after 3 and 6 months. RESULTS: Serum cholesterol and triglycerides decreased to the same extent (29 and 21% respectively) in both groups. Serum tocopherol decreased by 18% in AP and increased by 50% in AE (P < 0.0001, between-group comparison by repeated measures ANOVA) but relative to lipids it increased by 15% in AP and by 100% in AE. Copper-induced production of thiobarbituric reactive substances in the LDL + VLDL fraction increased by 18% in AP and did not change in AE (P = 0.02). The lagtime for the production of fluorescent products was prolonged by 13 min only in group AE (P = 0.028). Plasma malondialdehyde decreased by 35% in both groups (P = 0.002) but not when adjusted for lipids. CONCLUSIONS: In T1DM Vitamin E supplements do not affect the lowering of lipids and plasma malondialdehyde achieved by Atorvastatin. They reverse the increase of in vitro peroxidation caused by Atorvastatin but do not achieve the decreases observed in patients not receiving lipid-lowering drugs. These results indicate that the antioxidant effect of Vitamin E is attenuated when given in conjunction with this statin.
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Antioxidantes/administración & dosificación , Diabetes Mellitus Tipo 1/metabolismo , Suplementos Dietéticos , Ácidos Heptanoicos/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Peroxidación de Lípido/efectos de los fármacos , Pirroles/administración & dosificación , alfa-Tocoferol/administración & dosificación , Adulto , Anciano , Atorvastatina , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Humanos , Lipoproteínas/efectos de los fármacos , Lipoproteínas/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Parietal cell antibodies (PCAs) are found in 20% of type 1 diabetic patients, denoting autoimmune gastritis and pernicious anemia, which may predispose to enterochromaffin-like (ECL) cell hyper/dysplasia and gastric carcinoid tumors. We evaluated whether chromogranin A (CgA), 5-hydroxyindole acetic acid (5-HIAA), and neuron-specific enolase (NSE) contribute to screening for ECL cell hyper/dysplasia. RESEARCH DESIGN AND METHODS: Sera from 93 type 1 diabetic patients (53 men and 40 women, 31 PCA(+) and 62 PCA(-), aged 45 +/- 13 years) were analyzed for PCAs by indirect immunofluorescence and for CgA, NSE, and gastrin by radioimmunoassay. Urinary 5-HIAA was tested by high-performance liquid chromatography. Corpus atrophy and ECL cell proliferation were assessed in gastric biopsies. RESULTS: PCA(+) patients had higher gastrin (P < 0.0001) and CgA levels (P = 0.003) and were more prone to autoimmune gastritis (odds ratio [OR] 17, P < 0.0001) and ECL cell hyper/dysplasia (OR = 23, P = 0.005) than PCA(-) subjects. ECL cell hyper/dysplasia was present in seven PCA(+) patients who showed higher CgA levels (P < 0.0001) than subjects without ECL cell hyper/dysplasia, but NSE and 5-HIAA levels were similar. CgA levels correlated with gastrinemia (r = 0.50, P < 0.0001), PCA titer (r = 0.42, P = 0.001), and 5-HIAA levels (r = 0.38, P = 0.012). Logistic regression identified the CgA level (beta = 0.01, P = 0.027) as an independent risk factor for ECL cell hyper/dysplasia when PCA, CgA, 5-HIAA, NSE, gastrin, sex, and age were tested. Multivariate linear regression demonstrated that CgA level was determined by ECL cell density (r = 0.59, P < 0.0001) and gastrin level (r = 0.67, P = 0.02). One PCA(+) patient with elevated gastrin, CgA, and 5-HIAA levels had a gastric carcinoid tumor. CONCLUSIONS: PCA(+) patients, particularly those with high gastrin and CgA levels, risk developing ECL cell hyper/dysplasia. The determination of CgA, but not NSE and 5-HIAA, may complement histology in evaluating ECL cell mass.
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Biomarcadores de Tumor/sangre , Cromograninas/sangre , Diabetes Mellitus Tipo 1/sangre , Células Enterocromafines/fisiología , Ácido Hidroxiindolacético/sangre , Tumores Neuroendocrinos/sangre , Autoanticuerpos/sangre , Cromogranina A , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/patología , Células Enterocromafines/patología , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/aislamiento & purificación , Humanos , Hiperplasia , Masculino , Persona de Mediana Edad , Fosfopiruvato Hidratasa/sangreRESUMEN
Blood glucose, lipids, alpha-tocopherol, and malondialdehyde were monitored in type 1 diabetes mellitus patients for 8 hours after a standard fat-rich breakfast and lunch. Although glucose and triglycerides increased, alpha-tocopherol decreased and malondialdehyde increased in the postprandial phase. In the postabsorptive phase values returned to fasting levels. These results point to the possible relevance of postprandial alpha-tocopherol depletion and lipid peroxidation to an increased cardiovascular risk in these patients.
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Diabetes Mellitus Tipo 1/sangre , Alimentos , alfa-Tocoferol/sangre , Absorción , Adulto , Glucemia/análisis , Femenino , Humanos , Cinética , Lípidos/sangre , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
BACKGROUND: Patients with diabetes have an increased risk of both developing and dying from cardiovascular disease, and, currently, more aggressive lipid-lowering targets are being recommended for these patients. Statins are widely and successfully used to correct dyslipidemia and prevent acute coronary episodes, but their effects on lipoprotein composition and peroxidation have not been fully investigated. We aimed to address this issue in type 1 diabetes mellitus. METHODS: T1DM patients with atherogenic index (total/HDL-cholesterol > 4) were randomised double-blindly to group A (n = 12) that received Atorvastatin 40 mg/day and group P (n = 12) that received placebo. They were monitored for blood biochemistry, LDL sub-fractions and lipid peroxidation at inclusion, after 6 and after 12 weeks. RESULTS: In group A, the 40% decrease in serum total and LDL cholesterol and 20% decrease in triglycerides was accompanied by a decrease in serum alpha-tocopherol from 46.4 +/- 16.3 (mean +/- SD) at inclusion to 32.2 +/- 11.8 and 32.6 +/- 14.0 micromol/L after 6 and 12 weeks respectively (p < 0.001 compared to group P by repeated-measures ANOVA). Relative to LDL + VLDL cholesterol, alpha-tocopherol increased by 40% (p < 0.001). Copper-induced LDL + VLDL peroxidation increased from 4891 +/- 1325 at inclusion to 6821 +/- 2291 and 7040 +/- 1712 nmol TBARS/mg LDL + VLDL cholesterol produced in 3 h (p = 0.004). LDL sub-fractions shifted towards the less dense regions (p = 0.03). CONCLUSIONS: These results suggest that Atorvastatin lowers the antioxidant capacity of LDL and VLDL in T1DM. The mechanisms underlying these changes merit further investigation and should be taken into account when planning long-term primary prevention of CHD in diabetes.
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Diabetes Mellitus Tipo 1/fisiopatología , Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Peroxidación de Lípido/efectos de los fármacos , Lípidos/sangre , Lipoproteínas LDL/sangre , Pirroles/uso terapéutico , Adulto , Edad de Inicio , Anciano , Atorvastatina , Índice de Masa Corporal , Diabetes Mellitus Tipo 1/sangre , Método Doble Ciego , Ayuno , Femenino , Humanos , Lipoproteínas LDL/efectos de los fármacos , Masculino , Persona de Mediana Edad , Placebos , Sustancias Reactivas al Ácido Tiobarbitúrico/análisisRESUMEN
OBJECTIVE: Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals. RESEARCH DESIGN AND METHODS: This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively. RESULTS: After 6 months, comparable HbA(1c) levels were found between the two treatment groups. Fasting plasma glucose tended to be lower in patients treated with insulin detemir, but this difference was not statistically significant (-0.76 mmol/l, P = 0.097). Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin (SD 3.37 vs. 3.78 mmol/l, P < 0.001). Risk of hypoglycemia was 22% lower with insulin detemir than with NPH insulin (P < 0.05) and 34% lower for nocturnal (2300-0600) hypoglycemia (P < 0.005). Nightly plasma glucose profiles were smoother and more stable with insulin detemir (P = 0.05). Body weight was significantly lower with insulin detemir at the end of the trial (P < 0.001). CONCLUSIONS: Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin.
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Glucemia/metabolismo , Proteínas Portadoras/administración & dosificación , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Insulina Isófana/efectos adversos , Insulina/administración & dosificación , Insulina/efectos adversos , Adulto , Peso Corporal , Proteínas Portadoras/efectos adversos , Diabetes Mellitus Tipo 1/sangre , Ingestión de Alimentos , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/epidemiología , Hipoglucemiantes/administración & dosificación , Incidencia , Insulina/análogos & derivados , Insulina Aspart , Insulina Detemir , Insulina Isófana/administración & dosificación , Insulina de Acción Prolongada , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVE: Approximately 15-20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs) targeting gastric H+/K+ATPase. We examined whether iron deficiency anemia, pernicious anemia, and autoimmune gastritis, which may predispose to gastric tumors, were more frequent in PCA+ than in PCA- patients. RESEARCH DESIGN AND METHODS: Gastric biopsies from 88 consecutively recruited type 1 diabetic patients (51 men and 37 women, 47 PCA+ and 41 PCA-, aged 42 +/- 13 years) were evaluated using the updated Sydney system. Immunostaining was done for parietal cells, B- and T-cells, enterochromaffin-like (ECL) cells, and Helicobacter pylori (HP). PCAs were assayed by indirect immunofluorescence, H+/K+ATPase antibodies by enzyme immunoassay, and HP by serology, urea breath test, and histology. Pentagastrin tests were performed in 42 subjects. RESULTS: Autoimmune gastritis (AG) was present in 57% of PCA+ and 10% of PCA- cases (OR 12.5, P < 0.0001). PCA positivity (beta = 1.44; P = 0.04) and hypergastrinemia (beta = 0.01; P = 0.026), but not HP, age, diabetes duration, sex, and HLA-DQ type were risk factors for AG. Iron deficiency anemia (OR 3.9, P = 0.015), pernicious anemia (OR = 4.6, P = 0.022), and hypochlorhydria (OR = 20.0, P = 0.0002) were more frequent in AG+ individuals. HP infection was present in 47 patients but did not influence corpus histology or gastrinemia. (Pre)malignant lesions were found in 26% of PCA+ subjects: ECL cell hyperplasia in 7 AG+ patients, comprising 1 with a gastric carcinoid tumor, and corpus intestinal metaplasia in 11 AG+ patients, including 1 with linitis plastica. CONCLUSIONS: PCA+ type 1 diabetic patients should be screened for autoimmune gastritis, iron deficiency, and pernicious anemia. Particularly hypergastrinemic PCA+ patients with autoimmune gastritis are at increased risk for (pre)malignant gastric lesions.
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Diabetes Mellitus Tipo 1/epidemiología , Gastritis Atrófica/epidemiología , Gastritis Atrófica/inmunología , Células Parietales Gástricas/inmunología , Adulto , Autoanticuerpos/sangre , Biopsia , Diabetes Mellitus Tipo 1/inmunología , Femenino , Gastritis Atrófica/patología , Infecciones por Helicobacter/epidemiología , Helicobacter pylori , Humanos , Masculino , Persona de Mediana Edad , Células Parietales Gástricas/patología , Prevalencia , Factores de RiesgoRESUMEN
We investigated inaugural disease phenotype in relation to the presence or absence of diabetes-associated autoantibodies and human leukocyte antigen (HLA) DQ risk genotypes in adult-onset diabetic patients. Blood samples and questionnaires were obtained from 1584 recent-onset Belgian Caucasian patients (age 15-39 yr at diagnosis of primary diabetes) who were recruited by the Belgian Diabetes Registry over an 11-yr period. At clinical diagnosis, antibody-positive patients (n = 1198) were on average younger and had more symptoms, a more acute disease onset, lower body mass index, and random C-peptide levels, but higher insulin needs, glycemia, and prevalence of ketonuria, HLA-DQ, and 5' insulin gene susceptibility genotypes (P < 0.001 vs. antibody-negative patients; n = 386). In antibody-positive patients, these characteristics did not differ according to HLA-DQ genotype. However, in antibody-negative subjects, we found that patients were younger (P = 0.001); had a lower body mass index (P < 0.001), higher insulin needs (P = 0.014), and amylasemia (P = 0.001); and tended to have a higher glycemia and lower C-peptide in the presence of susceptible HLA-DQ genotypes. Differences according to HLA-DQ genotype subsisted after careful age-matching. In conclusion, we found no relation between initial disease phenotype and HLA-DQ genotype in antibody-positive diabetic young adults. In contrast, antibody-negative patients displayed more type 1-like features when carrying susceptible HLA-DQ genotypes known to promote the development of antibody-positive diabetes. The overrepresentation of these susceptibility genotypes in antibody-negative patients suggests the existence of an immune-mediated disease process with as yet unidentified immune markers in a subgroup of seronegative patients.
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Diabetes Mellitus/genética , Diabetes Mellitus/inmunología , Antígenos HLA-DQ/genética , Adolescente , Adulto , Autoanticuerpos/análisis , Diabetes Mellitus/fisiopatología , Femenino , Genotipo , Humanos , Masculino , FenotipoRESUMEN
OBJECTIVE: A worldwide increase in the incidence of childhood type 1 diabetes has been observed. Because in various countries the majority of new type 1 diabetic patients are diagnosed in adulthood, we investigated whether the rising incidence of this disorder in children reflects a global increase in the incidence of diabetes or a shift toward earlier clinical presentation. RESEARCH DESIGN AND METHODS: The incidence of type 1 diabetes presenting before age 40 years was prospectively measured in the Antwerp district over a 12-year period (1989-2000). The completeness of ascertainment was evaluated by the capture-recapture method. Trends in incidence during the study period were analyzed by Poisson regression. RESULTS: The incidence of type 1 diabetes diagnosed before age 40 years remained constant over the 12-year period, averaging 9.9 cases per 100,000 individuals per year. The incidence was similar in both sexes under age 15 years, but a marked male excess was noted for adult-onset disease, in particular after age 20 years, resulting in a male-to-female ratio of 0.9 under age 15 years vs. 1.6 thereafter (P = 0.001). During the 12-year observation period, there was a significant tendency toward increasing incidence under age 15 years at the expense of a decreasing incidence between ages 15 and 40 years (P = 0.025). The annual increase in incidence averaged 1.8% under age 15 years and 5.0% under age 5 years (P = 0.06). CONCLUSIONS: Our results indicate that in Belgium, the increasing incidence of childhood type 1 diabetes-especially for children under age 5 years-is not attributable to a global increase in disease incidence, but rather to earlier clinical manifestation. The results suggest that an environmental factor may preferentially accelerate the subclinical disease process in young diabetes-prone subjects.
Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Adulto , Distribución por Edad , Bélgica/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Análisis de Regresión , Distribución por Sexo , Factores de TiempoRESUMEN
OBJECTIVE: Delayed gastric emptying and/or gastrointestinal symptoms occur in 30-50% of diabetic patients. Known contributing factors are autonomic neuropathy and acute hyperglycemia, but the role of gastric autoimmunity has never been investigated, although 15-20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs). We studied gastric motility in diabetes in relation to PCA status, autonomic nerve function, HbA(1c), thyroid-stimulating hormone (TSH), Helicobacter pylori (HP), acid production, and gastric histology. RESEARCH DESIGN AND METHODS: Gastric emptying of solids and liquids (measured by (13)C-octanoic acid and (13)C-glycine breath tests, respectively) was tested in euglycemic conditions in 42 type 1 diabetic patients (male/female: 29/13; 15 PCA+; mean age 40 +/- 15 years; mean HbA(1c) 7.8 +/- 0.9%). Gastrointestinal symptoms, autonomic nerve function (Ewing tests), PCA status (indirect immunofluorescence), gastric histology, and acid secretion (pentagastrin) were assessed. RESULTS: Solid gastric emptying was delayed in 40% and liquid emptying in 36% of patients. Gastric motility did not correlate with symptoms. PCA status, gastric morphology, and acid secretion were similar in those with and without gastroparesis. HbA(1c) level (beta = 1.34, P = 0.011) was the only risk factor for delayed solid emptying in a logistic regression model testing HbA(1c), autonomic nerve function, PCA, HP status, age, sex, diabetes duration, and TSH. Half-emptying time for liquids correlated with TSH level (r = 0.83, P < 0.0001) and autonomic neuropathy score (r = -0.79, P = 0.001). CONCLUSIONS: We found that approximately 50% of type 1 diabetic patients studied had delayed gastric emptying that did not correlate with symptoms. Gastric autoimmunity did not contribute to diabetic gastroparesis. Metabolic control was worse in patients with delayed solid emptying.